What is the recommended treatment approach for a patient presenting with non-Hodgkin lymphoma (NHL)?

Non-Hodgkin Lymphoma: Clinical Manifestations and Treatment Approach

Clinical Presentation

Non-Hodgkin lymphoma typically presents as painless, persistent lymphadenopathy, though systemic B symptoms (fever, unexplained weight loss >10%, drenching night sweats) occur in more advanced disease stages. 1, 2

• Patients may present with involvement of extranodal sites beyond the lymphoid system 3
• Constitutional symptoms indicate more advanced disease and affect staging 2
• Diffuse large B-cell lymphoma (DLBCL) represents 30-58% of NHL cases, with incidence increasing dramatically with age from 0.3/100,000 at ages 35-39 to 26.6/100,000 at ages 80-84 4

Diagnostic Workup

An excisional lymph node biopsy providing adequate tissue for histopathology and immunohistochemistry is mandatory for proper diagnosis—fine needle aspiration or core biopsy is inadequate except in rare emergency situations. 1, 5

Required Tissue Analysis

• Formalin-fixed samples with fresh frozen material for molecular characterization 4
• Immunohistochemistry must include CD20 status 4, 1
• Histological classification per WHO criteria, specifically excluding Burkitt and mantle cell lymphoma 4
• Processing by an experienced pathology institute is essential 4

Staging Evaluation

Complete staging requires CT scan of chest, abdomen, and pelvis, bone marrow aspirate and biopsy, complete blood count, LDH, uric acid, and screening for HIV, hepatitis B, and hepatitis C. 1

• Ann Arbor staging system with notation of bulky disease (>10 cm) 4, 1
• International Prognostic Index (IPI) must be calculated for large cell lymphomas 4, 1
• Diagnostic lumbar puncture with prophylactic intrathecal cytarabine/methotrexate for high-risk patients (IPI >2) with bone marrow, testicular, spinal, or skull base involvement 4, 6
• PET-CT is preferred when available for accurate staging of FDG-avid lymphomas 5

Treatment Strategy

Six to eight cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given every 21 days is the standard treatment for CD20-positive large B-cell NHL of all stages. 4, 1, 5

Treatment Stratification

Treatment should be stratified by IPI score and patient factors 1, 5:

• Young low-risk patients (IPI 0-1): Standard R-CHOP
• Young high-risk patients (IPI ≥2): Standard R-CHOP (high-dose chemotherapy with stem cell transplant as first-line remains experimental) 4
• Elderly patients: R-CHOP with dose adjustments as needed

Critical Treatment Principles

• Dose reductions for hematological toxicity should be avoided to maintain treatment efficacy 4, 6
• Prophylactic G-CSF is justified for febrile neutropenia in patients treated with curative intent 4, 6
• R-CHOP can be given every 14 days with growth factor support as an alternative 4
• Rituximab depletes CD19-positive B cells within three weeks, with sustained depletion for 6-9 months 7

Tumor Lysis Syndrome Prevention

In patients with high tumor burden, implement special precautions 4:

• Prephase treatment with corticosteroids 6
• Aggressive hydration and allopurinol or rasburicase
• Close monitoring of electrolytes and renal function

Role of Radiotherapy

Consolidation radiotherapy to sites of bulky disease has not proven benefit and is not routinely recommended. 4

• Involved-field radiotherapy may be considered for limited-stage disease after abbreviated chemotherapy, though this remains controversial 5

Response Evaluation

Radiological assessment should be performed after 2-4 cycles, after completion of treatment, and whenever response is questioned. 1, 6

• PET-CT is preferred for response assessment in FDG-avid lymphomas 5
• Bone marrow biopsy or lumbar puncture repeated only if initially involved 4
• Patients with incomplete or inadequate response should be immediately evaluated for salvage regimens 1

Relapsed/Refractory Disease

For chemosensitive relapsed disease, high-dose chemotherapy with autologous stem cell transplantation is standard 5, 8:

• Salvage regimens (DHAP, IGEV, ICE) used before transplant 5
• Novel agents (brentuximab vedotin, nivolumab, pembrolizumab) for post-transplant relapse 5

Surveillance and Follow-up

History, physical examination, blood count, and LDH at 3,6,12, and 24 months, then only as clinically indicated for patients suitable for further therapy. 4, 6

• CT scans at 6,12, and 24 months after treatment completion 6
• Thyroid function monitoring (TSH) at 1,2, and 5 years if neck irradiation received 4, 6
• Monitor for long-term chemotherapy toxicities including secondary malignancies 4

Critical Pitfalls to Avoid

• Never rely on fine needle aspiration alone—inadequate tissue prevents proper subtyping 1
• Never reduce chemotherapy doses for hematological toxicity—use G-CSF support instead 4, 6
• Never skip CNS prophylaxis in high-risk patients—intrathecal therapy at first diagnostic LP prevents CNS relapse 4, 6
• Screen for hepatitis B before rituximab—reactivation can be fatal 1
• Elderly patients (≥70 years) have higher rates of grade 3-4 neutropenia, anemia, and infections with R-CHOP 7